Growth hormone releasing hormone (GHRH), also known as growth hormone releasing factor (GRF or GHRF), is a 44-amino acid peptide secreted from neurons innervating anterior pituitary and elicits growth hormone (GH; also known as somatotropin) secretion from somatotroph cells. The minimally bioactive conformation of the GHRH peptide was identified to be present in the first 29 amino acids of the full length peptide (Frohman et al., 1986a), though low potency biological activity can be detected in GHRH (1-21) (Ling et al 1984a); GHRH peptides shorter than 21 amino acids were found to be inactive. GH is a physiological anabolic agent that is involved in increasing linear growth, muscle, bone and cartilage mass, and reduction of fat mass. GH deficiency, or a decrease in GH secretion, is known to be associated with short stature in children, fat gain particularly in the deep abdominal depots and increased cardiovascular risk.
The therapeutic utility of GHRH is compromised by the proteolytic lability of the peptide; GHRH is rapidly inactivated by dipeptidyl peptidase IV (DPPIV) in vivo through a cleavage between Ala2-Asp3 (Frohman et al., 1986b) and other proteases at Arg11-Lys12 and Lys12-Val13 (Frohman et al 1989). Various approaches have been used in order to provide proteolytically stable analogues of GHRH, including amino acid substitutions, cyclization of amino acid side chains, and modification with synthetic polymers and fatty acids.
The present description refers to a number of documents, the contents of which are herein incorporated by reference in their entirety.